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KMID : 0357920070410010001
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Korean Journal of Pathology
2007 Volume.41 No. 1 p.1 ~ p.6
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Synergistic Apoptotic Effect of Combination Treatment with Troglitazone and COX-2 Inhibitor in Glioma Cells
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Kim Kyung-Ryoul
Park Min-Young
Park Ho-Sung
Jang Kyu-Yun
Moon Woo-Sung
Lee Dong-Geun
Kang Myoung-Jae
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Abstract
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Background : The use of troglitazone (a PPARγ ligand) and COX-2 inhibitor have been intensively studied for inhibition of tumor growth in cancer treatment, but the anti-tumor effect with a combination of these agents for cancer has not yet been studied. The aim of this study was to determine if low concentrations of troglitazone with COX-2 inhibitor in combination would cause significant cytotoxicity in glioma cells.
Methods : The effects of co-treatment with troglitazone and COX-2 inhibitor on cell growth and apoptosis were assessed by use of trypan blue exclusion and a DNA fragmentation assay. A western blot was used to analyze the apoptotic signaling for the expression of bcl-2, bax, PARP and p21 proteins.
Results : A low dose of troglitazone (5μM) and COX-2 inhibitor (5μM) strongly enhanced the cell growth inhibition and apoptosis in glioma cells when compared to a low dose of each drug alone. Western blotting analysis showed a decreased expression of bcl-2 and PARP proteins. In contrast, the bax protein level was increased.
Conclusions : The combination of troglitazone and COX-2 inhibitor in a low dose elicits synergistic cytotoxicity in glioma cells. Our study also demonstrates that down regulation of bcl-2, fragmentation of PARP protein and increased expression of bax protein were accompanied by co-treatment with troglitazone and the COX-2 inhibitor.
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KEYWORD
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Troglitazone, Cyclooxygenase-2, Glioma, Apoptosis
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